Schizophrenia
Conditions
Brief summary
The purpose of this study is to evaluate whether ITI-007 is effective in reducing symptoms associated with schizophrenia in patients who are having an acute worsening of their psychosis. Patients will be randomly assigned to receive one of two doses of ITI-007, placebo, or a positive control. The primary goal will be to assess the effects of ITI-007 on psychosis. The safety of ITI-007 will also be assessed.
Detailed description
The study will be conducted as a randomized, double-blind, placebo-controlled, multi-center study in patients diagnosed with schizophrenia and an acute exacerbation of psychosis. The efficacy and safety of two dose levels of ITI-007 administered daily for 28 days will be evaluated as compared to placebo; risperidone has been included as a positive control. Upon completion of the inpatient 28-day Study Treatment Period, patients will be started on standard antipsychotic medication and will be stabilized over a 5-day period before discharge from the study clinic. Patients will be seen for a final outpatient safety evaluation at the End-of-Study visit approximately 2 weeks after discharge.
Interventions
DRUGITI-007
Capsules containing ITI-007 for 28 days
DRUGPlacebo
Capsules containing inactive placebo for 28 days
DRUGRisperidone
Capsules containing risperidone for 28 days
Sponsors
Intra-Cellular Therapies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Patient's age is 18-55 * Patient has current diagnosis of schizophrenia and is experiencing an acute exacerbation of psychosis * Patient has a history of at least three months exposure to one or more antipsychotic therapy(ies) and a prior response to antipsychotic therapy within the previous five years
Exclusion criteria
* Any female patient who is pregnant or breast-feeding * Any patient presenting with concurrent dementia, delirium, mental retardation, epilepsy, drug-induced psychosis, or history of significant brain trauma * Any patient presenting with schizoaffective disorder, bipolar disorder, acute mania, or major depression with psychotic features * Any patient considered to be an imminent danger to themselves or others * Any patient with hematological, renal, hepatic, endocrinological, neurological, or cardiovascular disease or substance abuse as defined by protocol * Any patient judged by the Investigator to be inappropriate for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 28 in Positive and Negative Syndrome Scale (PANSS) Total Score | Change from baseline to Day 28 | The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 8 in Positive and Negative Syndrome Scale (PANSS) Total Score | Change from Baseline to Day 8 | The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms. |
| Change From Baseline to Day 15 in Positive and Negative Syndrome Scale (PANSS) Total Score | Change from Baseline to Day 15 | The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms. |
| Change From Baseline to Day 22 in Positive and Negative Syndrome Scale (PANSS) Total Score | Change from Baseline to Day 22 | The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) Lumateperone 42 mg (ITI-007 60 mg tosylate) administered for 28 days
Lumateperone 42 | 84 |
| Lumateperone 84 mg (ITI-007 120 mg Tosylate) Lumateperone 84 mg (ITI-007 120 mg tosylate) administered for 28 days
Lumateperone 84 | 83 |
| Placebo Placebo: Capsules containing inactive placebo administered for 28 days | 85 |
| Risperidone 4 mg Risperidone: Capsules containing 4 mg risperidone administered for 28 days | 82 |
| Total | 334 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 1 | 3 |
| Overall Study | Lack of Efficacy | 0 | 1 | 6 | 3 |
| Overall Study | Other | 8 | 6 | 6 | 4 |
| Overall Study | Physician Decision | 2 | 1 | 3 | 0 |
| Overall Study | Specific Request of Sponsor or Investigator | 2 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 10 | 11 | 7 | 8 |
Baseline characteristics
| Characteristic | Total | Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Lumateperone 84 mg (ITI-007 120 mg Tosylate) | Placebo | Risperidone 4 mg |
|---|---|---|---|---|---|
| Age, Continuous | 40.1 years STANDARD_DEVIATION 9.56 | 38.3 years STANDARD_DEVIATION 10.03 | 41.4 years STANDARD_DEVIATION 8.92 | 40.5 years STANDARD_DEVIATION 9.83 | 40.7 years STANDARD_DEVIATION 9.33 |
| Positive and Negative Syndrome Scale (PANSS) Total Score | 86.2 units on a scale STANDARD_DEVIATION 12.04 | 88.1 units on a scale STANDARD_DEVIATION 11.04 | 84.6 units on a scale STANDARD_DEVIATION 11.63 | 86.3 units on a scale STANDARD_DEVIATION 13.1 | 86.1 units on a scale STANDARD_DEVIATION 12.24 |
| Race/Ethnicity, Customized Asian | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 261 Participants | 70 Participants | 62 Participants | 65 Participants | 64 Participants |
| Race/Ethnicity, Customized Caucasian/White | 62 Participants | 13 Participants | 16 Participants | 17 Participants | 16 Participants |
| Race/Ethnicity, Customized Other | 9 Participants | 1 Participants | 5 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Female | 58 Participants | 18 Participants | 11 Participants | 20 Participants | 9 Participants |
| Sex: Female, Male Male | 276 Participants | 66 Participants | 72 Participants | 65 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 83 | 0 / 85 | 0 / 82 |
| other Total, other adverse events | 39 / 84 | 52 / 83 | 28 / 85 | 37 / 82 |
| serious Total, serious adverse events | 0 / 84 | 0 / 83 | 1 / 85 | 1 / 82 |
Outcome results
Primary
Change From Baseline to Day 28 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms.
Time frame: Change from baseline to Day 28
Population: The study was powered for prespecified comparison of both doses of ITI-007 with placebo using a Bonferroni correction for multiple comparisons. The study was not statistically powered to include multiple comparisons of risperidone to placebo and thus, the risperidone 4mg treatment group was included in the model fitting but was not included in the adjustment for multiplicity or primary outcomes determination.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Change From Baseline to Day 28 in Positive and Negative Syndrome Scale (PANSS) Total Score | -13.2 score on a scale | Standard Error 1.7 |
| Lumateperone 84 mg (ITI-007 120 mg Tosylate) | Change From Baseline to Day 28 in Positive and Negative Syndrome Scale (PANSS) Total Score | -8.3 score on a scale | Standard Error 1.7 |
| Placebo | Change From Baseline to Day 28 in Positive and Negative Syndrome Scale (PANSS) Total Score | -7.4 score on a scale | Standard Error 1.7 |
| Risperidone 4 mg | Change From Baseline to Day 28 in Positive and Negative Syndrome Scale (PANSS) Total Score | -13.4 score on a scale | Standard Error 1.7 |
Comparison: The study was powered for prespecified comparison of both doses of ITI-007 with placebo using a Bonferroni correction for multiple comparisons. The study was not statistically powered to include multiple comparisons of risperidone to placebo and thus, this comparison is not presented here.p-value: 0.01795% CI: [-11.1, -0.4]Mixed Effects model for Repeated Measure
Comparison: The study was powered for prespecified comparison of both doses of ITI-007 with placebo using a Bonferroni correction for multiple comparisons. The study was not statistically powered to include multiple comparisons of risperidone to placebo and thus, this comparison is not presented here.p-value: 0.70895% CI: [-6.3, 4.5]Mixed Effects Model for Repeated Measure
Secondary
Change From Baseline to Day 15 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms.
Time frame: Change from Baseline to Day 15
Population: ITT Population with LOCF
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Change From Baseline to Day 15 in Positive and Negative Syndrome Scale (PANSS) Total Score | -7.8 units on a scale | Standard Error 1.4 |
| Lumateperone 84 mg (ITI-007 120 mg Tosylate) | Change From Baseline to Day 15 in Positive and Negative Syndrome Scale (PANSS) Total Score | -4.2 units on a scale | Standard Error 1.3 |
| Placebo | Change From Baseline to Day 15 in Positive and Negative Syndrome Scale (PANSS) Total Score | -4.5 units on a scale | Standard Error 1.3 |
| Risperidone 4 mg | Change From Baseline to Day 15 in Positive and Negative Syndrome Scale (PANSS) Total Score | -9.6 units on a scale | Standard Error 1.4 |
Secondary
Change From Baseline to Day 22 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms.
Time frame: Change from Baseline to Day 22
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Change From Baseline to Day 22 in Positive and Negative Syndrome Scale (PANSS) Total Score | -10.5 units on a scale | Standard Error 1.6 |
| Lumateperone 84 mg (ITI-007 120 mg Tosylate) | Change From Baseline to Day 22 in Positive and Negative Syndrome Scale (PANSS) Total Score | -6.6 units on a scale | Standard Error 1.5 |
| Placebo | Change From Baseline to Day 22 in Positive and Negative Syndrome Scale (PANSS) Total Score | -4.6 units on a scale | Standard Error 1.5 |
| Risperidone 4 mg | Change From Baseline to Day 22 in Positive and Negative Syndrome Scale (PANSS) Total Score | -10.8 units on a scale | Standard Error 1.6 |
Secondary
Change From Baseline to Day 8 in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS is a 30-item scale used to measure symptoms of schizophrenia. The scale has 7 positive symptom items, 7 negative symptom items, and 16 general psychopathology symptom items. Each item is scored on a 7-point scale by the clinical rater based on a clinical interview with the patient, with a score of 1 indicating the absence of symptoms and a score of 7 indicating extremely severe symptoms. Thus, the PANSS Total score minimum is 30 and the maximum is 210, with higher numbers indicating more severe symptoms.
Time frame: Change from Baseline to Day 8
Population: ITT Population with LOCF
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Lumateperone 42 mg (ITI-007 60 mg Tosylate) | Change From Baseline to Day 8 in Positive and Negative Syndrome Scale (PANSS) Total Score | -4.0 units on a scale | Standard Error 1.2 |
| Lumateperone 84 mg (ITI-007 120 mg Tosylate) | Change From Baseline to Day 8 in Positive and Negative Syndrome Scale (PANSS) Total Score | -4.7 units on a scale | Standard Error 1.2 |
| Placebo | Change From Baseline to Day 8 in Positive and Negative Syndrome Scale (PANSS) Total Score | -2.6 units on a scale | Standard Error 1.2 |
| Risperidone 4 mg | Change From Baseline to Day 8 in Positive and Negative Syndrome Scale (PANSS) Total Score | -6.3 units on a scale | Standard Error 1.2 |